Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000611439 | SCV001000056 | likely benign | Hereditary pancreatitis | 2023-11-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000611439 | SCV001185412 | benign | Hereditary pancreatitis | 2015-01-07 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174692 | SCV001337944 | likely benign | not specified | 2021-01-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000611439 | SCV002534764 | benign | Hereditary pancreatitis | 2019-12-09 | criteria provided, single submitter | curation | |
ARUP Laboratories, |
RCV000611439 | SCV004562804 | uncertain significance | Hereditary pancreatitis | 2023-08-07 | criteria provided, single submitter | clinical testing | The PRSS1 c.508A>G; p.Lys170Glu variant (rs201550522) is reported in one patient of Indian heritage with a clinical diagnosis of hereditary pancreatitis (Rebours 2009); and in two individuals with tropical calcific pancreatitis (TCP; Paliwal 2016). In addition, a single functional study on p.Lys170Glu showed approximately a 30 percent increased trypsinogen secretion and enzyme activity level (Schnur 2014), suggesting that this variant is likely to confer an increased risk for pancreatitis. This variant is also reported in ClinVar (Variation ID: 518381). It is observed in the general population with an overall allele frequency of 0.03% (49/152158 alleles, including 2 homozygotes) in the Genome Aggregation Database (gnomAD v3.1.2). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.284). Based on the available information, the clinical significance of this variant is uncertain at this time. References: Paliwal S et al. Association Analysis of PRSS1-PRSS2 and CLDN2-MORC4 Variants in Nonalcoholic Chronic Pancreatitis Using Tropical Calcific Pancreatitis as Model. Pancreas. 2016 Sep;45(8):1153-7. PMID: 26784911. Rebours V et al. The natural history of hereditary pancreatitis: a national series. Gut. 2009 Jan;58(1):97-103. PMID: 18755888. Schnur A et al. Functional effects of 13 rare PRSS1 variants presumed to cause chronic pancreatitis. Gut. 2014 Feb;63(2):337-43. PMID: 23455445. |